The candidate is a clinician/neuroscientist, whose research is focused on understanding how disturbances in the circuitry of the dorsolateral prefrontal cortex (DLPC) may contribute to the cognitive dysfunction that is characteristic of schizophrenia. The candidate's career goals include 1) to further develop the research skills and approaches necessary to identify the pathophysiological processes operative in schizophrenia, 2) to participate in the training and career development of the next generation of translational neuroscientists, and 3) to lead a multidisciplinary group of scientists in the study of schizophrenia. These goals will be pursued in the context of an NIMH-funded Center for Neuroscience of Mental Disorders at the University of Pittsburgh, directed by the candidate, which is entitled "Cortical Circuitry and Cognition in Schizophrenia." The resources of the Center, and the extensive interactions that occur among its 26 basic and clinical researchers, provide a rich environment for the continued development and expansion of the candidate's research activities. In the studies proposed in this application, the candidate will use a combination of anatomical and in vitro electrophysiological techniques in monkeys, and postmortem studies in humans, to test a series of hypotheses under the following four specific aims: 1) Characterization of the organization, synaptic targets and chemical identity of thalamic projections to monkey DLPFC; 2) Determination of the integrity of the projections from the medial dorsal thalamic nucleus to the DLPFC in subjects with schizophrenia; 3) Characterization of intrinsic connectivity of monkey DLPFC , especially that involving the chandelier class of GABA neurons; and 4) Determination of the nature of DLPFC chandelier neuron abnormalities in schizophrenia. In addition, through research collaborations and consultations, the candidate will acquire skills in the application of new methodologies, such as gene arrays, to the study of DLPFC circuitry in schizophrenia. Thus, in addition to achieving specific research goals, the proposed studies and career development activities will enhance the candidate's performance and capacity as a clinician/scientist, research mentor, scientific leader and science educator and advocate.